The fetal liver is a major site of hematopoiesis during mid-gestation. It is a rich source of hematopoietic stem cells but contains few if any immunocompetant lymphocytes capable of inducing graft versus host disease. Transplantation of fetal liver cells results in full hematologic and immunologic reconstitution of lethally irradiated rodents, but has not been critically evaluated in large animals or in man. Fetal liver hematopoiesis differs in many ways from that occurring in adult bone marrow. Fetal liver is primarily an organ of erythropoiesis although pluripotent and granulocyte/macrophage progenitors are present as well. I propose to study the cellular interactions and humoral factors regulating fetal liver hematopoiesis in short term clonal assays of erythropoiesis and granulopoiesis and also in a recently developed long term culture system. The immunologic characteristics of fetal liver lymphoid cells will be evaluated in clonal assays of mitrogen responsive and alloreactive cells. Fetal liver cell transplantation will be evaluated in a dog model and the factors affecting engraftment, reconstitution and graft versus host disease will be assessed. Ultimately, human fetal liver cell transplantation will be evaluated in patients with bone marrow failure or hematologic malignancies.